Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P30536 (PBS)
 9,886 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The cytosolic members of the heat shock protein 70 (HSP-70) family have been shown to elicit protective cell mediated immunity in animal tumor models. The aim of this study was to investigate the effect of the HSP-70 enriched lysate of heated tumor cells as vaccines in cancer immunotherapy in the mouse model for WEHI-164 fibrosarcoma. Three animal bearing tumor groups were investigated: test group; vaccinated with enriched HSP-70 tumor lysate, control group I; vaccinated with tumor lysate only and control group II; received PBS. The results indicated that vaccinated mice in the test group had resulted in a significant reduction in tumor size and longer survival. To find the mechanism of these results, we measured the splenocytes proliferation, tumor infiltrated lymphocytes and cytotoxic activity of the splenocytes. The results indicated a significant increase in the proliferation of mouse splenocytes, a significant increase in the CD8+ lymphocytes as well as significant increase in the cytotoxic activity of splenocytes against the target cells in the test group. In addition, we analyzed the shifting of Th1/Th2 in all the groups. The results indicated a significant increase in the IFN-gamma production in the test group. These findings provided a useful therapeutic model for development of approaches to cancer treatments.
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PMID:Evaluation of anti-tumor effects of tumor cell lysate enriched by HSP-70 against fibrosarcoma tumor in BALB/c mice. 1749 94

The objective of this study was to assess the antiallergic effect of fermented milk prepared, respectively, with Streptococcus thermophilus MC, Lactobacillus acidophilus B, Lactobacillus bulgaricus Lb, L. bulgaricus 448, and Bifidobacterium longum B6. Female BALB/c mice fed fermented milk were immunized intraperitoneally with ovalbumin (OVA)/complete Freund's adjuvant (CFA) to evaluate the immune response by observing the secretion of cytokines IL-2, IL-4, and IFN-gamma and serum antibody IgE. The results showed that supplementation with lactic acid bacteria fermented milk did not significantly change the IL-2 spontaneous and OVA-stimulated secretions of splenocytes. However, both spontaneous and OVA-stimulated secretions of splenocytes from mice fed lactic acid bacteria fermented milk showed significantly (P < 0.05) lower levels of IL-4 (Th2 cytokine) than those from OVA/CFA-immunized mice fed non-fermented milk (OVA/CFA-milk group). The spontaneous secretion of IFN-gamma (Th1 cytokine) by splenocytes from mice fed L. bulgaricus 448 or L. bulgaricus Lb fermented milk significantly increased as compared to that from the OVA/CFA-milk group. The results showed that the ratios of IFN-gamma to IL-4 of both spontaneous and OVA-stimulated secretions in splenocytes from mice fed lactic acid bacteria fermented milk increased significantly as compared to that of PBS- or OVA/CFA-milk groups. The serum levels of OVA-specific IgE in fermented milk fed groups, especially the group fed S. thermophilus MC fermented milk, were significantly lower than those in the OVA/CFA-milk group through a 6 week feeding experiment. The results showed that milk fermented with lactic acid bacteria demonstrated in vivo antiallergic effects on OVA/CFA-immunized mice via increasing the secretion ratio of IFN-gamma/IL-4 (Th1/Th2) by splenocytes and decreasing the serum level of OVA-specific IgE.
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PMID:Antiallergic effect of milk fermented with lactic acid bacteria in a murine animal model. 1753 Aug 57

An impediment to the development of efficacious vaccines for bovine tuberculosis has been the failure to demonstrate strong associations between immune function and protective immunity. Cytokine gene expression in response to Mycobacterium bovis (M. bovis) infection was evaluated to identify correlates of immunity. Ten Holstein calves were infected with M. bovis by intratonsillar inoculation. Five uninfected animals served as controls. At 15, 30, 60 and 85 days post-infection (dpi) peripheral blood mononuclear cells (PBMC) were isolated and stimulated with either purified protein derivative of M. bovis (PPD), a recombinant fusion protein comprised of 6 kDa early secretory antigenic target and 10 kDa culture filtrate antigen (rESAT6:CFP10), or PBS. After a 16 h incubation period, total leukocyte RNA was isolated and gene expression evaluated using reverse transcriptase real-time PCR. In addition, gene expression adjacent to gross lesion in the retropharyngeal lymph node (LN) was analyzed. Pathology was evaluated at necropsy. Expression of IFN-gamma, TNF-alpha, iNOS and IL-4 by PBMC increased in response to infection, whereas, IL-10 expression decreased. Differences in gene expression between PBMC from infected and uninfected animals was greatest at 30 dpi. Infected animals were divided into two groups based on pathology. Animals in the low pathology group had lesions primarily in LN of the head; whereas, animals in the high pathology group also had lesions in the lungs and lung associated LN. Gene expression in PBMC and LN was compared between animals in the high and low pathology groups. Cells from animals in the high pathology group expressed more IFN-gamma, TNF-alpha, iNOS and IL-4 than did animals in the low pathology group at early time points. IL-10 gene expression decreased with time in PBMC from animals in the high pathology group. At 85 dpi, animals in the high pathology group expressed twofold less IL-10 mRNA than did animals in the low pathology group and the uninfected controls. IFN-gamma and iNOS gene expression were significantly greater in tissues from infected animals compared to tissues from uninfected animals. The pathological outcome of M. bovis infection of cattle may be established early after infection since expression of both the TH1 and TH2 cytokines were differentially expressed by animals in the high and low pathology groups at early time points. In addition, more robust immunological responses were associated with increased pathology. These results suggest that early immune responses play a critical role in establishing the pathological outcome.
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PMID:Associations between cytokine gene expression and pathology in Mycobacterium bovis infected cattle. 1762 95

CpG oligodeoxynucleotides (CpG ODN) are known to be a potent immunoadjuvant for a wide range of antigens. The aim of this study was to evaluate the role of CpG ODN co-encapsulated with rgp63 antigen in cationic liposomes (Lip-rgp63-CpG ODN) in immune response enhancement and protection in BALB/c mice against leishmaniasis. Lip-rgp63-CpG ODN prepared by using dehydration-rehydration vesicle (DRV) method significantly inhibited (P<0.001) Leishmania major infection in mice measured by footpad swelling compared to Lip-rgp63, rgp63 alone, rgp63 plus CpG ODN, PBS or control liposomes. The mice immunized with Lip-rgp63-CpG ODN also showed the lowest spleen parasite burden, highest IgG2a/IgG1 ratio and IFN-gamma production and the lowest IL-4 production compared to the other groups. The results indicate that co-encapsulation of CpG ODN in liposomes improves the immunogenicity of Leishmania antigen.
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PMID:The role of CpG ODN in enhancement of immune response and protection in BALB/c mice immunized with recombinant major surface glycoprotein of Leishmania (rgp63) encapsulated in cationic liposome. 1762 72

Scutellaria baicalensis Georgi is one of the important medicinal herbs widely used for the treatment of various inflammatory diseases in Asia. Baicalin (BA) is a bioactive anti-inflammatory flavone found abundantly in Scutellaria baicalensis Georgi. To explore the therapeutic potential of BA, we examined the effects of systemic administration of the flavone (5 and 10 mg/kg, ip) on relapsing/remitting experimental autoimmune encephalomyelitis (EAE) induced by proteolipid protein 139-151 in SJL/J mice, an experimental model of multiple sclerosis. The mice treated with PBS or BA at day -1 and for 3 consecutive days were observed daily for clinical signs of disease up to 60 days after immunization. In the PBS-EAE group, neurological scores were: incidence (100%), mean day of onset (8.0 +/- 0.73), peak clinical score (3.0 +/- 0.4), and cumulative disease index (141.8 +/- 19.4). In the BA-EAE group (5 or 10 mg kg(-1) day(-1), respectively), incidence (95 or 90%), mean day of onset (9.0 +/- 0.80 or 9.2 +/- 0.75; P = 0.000), peak clinical score (2.2 +/- 0.3 or 2.0 +/- 0.3; P = 0.000), and cumulative disease index (75.9 +/- 10.1 or 62.9 +/- 8.4; P = 0.000) decreased, accompanied by the histopathological findings (decrease of dense mononuclear infiltration surrounding vascellum) for the spinal cord. Additionally, the in vitro effects of BA (5, 10, and 25 microM) on mononuclear cells collected from popliteal and inguinal lymph nodes of day-10 EAE mice were evaluated using an MTT reduction assay for cell proliferation, and ELISA to measure IFN-gamma and IL-4 cytokines. Compared with the control group, BA caused an increase in IL-4 (EAE-DMSO: 3.56 +/- 0.42 pg/mL vs EAE-BA (5, 10, and 25 microM): 6.03 +/- 1.1, 7.83 +/- 0.65, 10.54 +/- 1.13 pg/mL, respectively; P < 0.001); but inhibited IFN-gamma (EAE-DMSO: 485.76 +/- 25.13 pg/mL vs EAE-BA (5, 10, and 25 microM): 87.08 +/- 9.24, 36.27 +/- 5.44, 19.18 +/- 2.93 pg/mL, respectively; P < 0.001) and the proliferation of mononuclear cells (EAE-DMSO: 0.73 +/- 0.021 vs EAE-BA (5, 10, and 25 microM): 0.41 +/- 0.015, 0.31 +/- 0.018, 0.21 +/- 0.11, respectively; P < 0.001) in a concentration-dependent manner. The results suggest that BA might be effective in the treatment of multiple sclerosis.
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PMID:Baicalin reduces the severity of experimental autoimmune encephalomyelitis. 1765 55

The glycosphingolipid alpha-galactosylceramide (alpha-GalCer) has been shown to be a potent activator of invariant NKT (iNKT) cells, rapidly inducing large amounts of both Th1 and Th2 cytokines upon injection in mice. The C-glycoside analog of alpha-GalCer (alpha-C-GalCer), by contrast, results in an enhanced Th1-type response upon activation of iNKT cells. We administered a single dose of these Ags to DBA/1 mice during the early induction phase of collagen-induced arthritis and demonstrated therapeutic efficacy of alpha-GalCer when administered early rather than late during the disease. Surprisingly, the Th1-polarizing analog alpha-C-GalCer also conferred protection. Furthermore, a biphasic role of IFN-gamma in the effect of iNKT cell stimulation was observed. Whereas in vivo neutralization of IFN-gamma release induced by either alpha-GalCer or alpha-C-GalCer early during the course of disease resulted in partial improvement of clinical arthritis symptoms, blockade of IFN-gamma release later on resulted in a more rapid onset of arthritis. Although no phenotypic changes in conventional T cells, macrophages, or APCs could be detected, important functional differences in T cell cytokine production in serum were observed upon polyclonal T cell activation, 2 wk after onset of arthritis. Whereas alpha-GalCer-treated mice produced significantly higher amounts of IL-10 upon systemic anti-CD3 stimulation compared with PBS controls, T cells from alpha-C-GalCer-treated mice, by contrast, produced substantially lower levels of cytokines, suggesting the involvement of different protective mechanisms. In conclusion, these findings suggest long-term, ligand-specific, time-dependent, and partially IFN-gamma-dependent immunomodulatory effects of iNKT cells in collagen-induced arthritis.
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PMID:A single early activation of invariant NK T cells confers long-term protection against collagen-induced arthritis in a ligand-specific manner. 1767 91

This study was undertaken to evaluate the effectiveness and mechanisms of anti-tumor activity of Baker's yeast, Saccharomyces cerevisiae, in immunocompetent mice. Swiss albino mice were inoculated intramuscularly in the right thigh with Ehrlich Ascites Carcinoma (EAC) cells. At day 8, mice bearing Solid Ehrlich Carcinoma tumor (SEC) were intratumorally (IT) injected with killed S. cerevisiae (10 x 10(6) and 20 x 10(6) cells) for 35 days. Histopathology of yeast-treated mice showed extensive tumor degeneration, apoptosis, and ischemic (coagulative) and liquefactive necrosis. These changes are associated with a tumor growth curve that demonstrates a significant antitumor response that peaked at 35 days. Yeast treatment (20 x 10(6) cells) three times a week resulted in a significant decrease in tumor volume (TV) (67.1%, P < 0.01) as compared to PBS-treated mice. The effect was determined to be dependent on dose and frequency. Yeast administered three and two times per week induced significant decrease in TV as early as 9 and 25 days post-treatment, respectively. Administration of yeast significantly enhanced the recruitment of leukocytes, including macrophages, into the tumors and triggered apoptosis in SEC cells as determined by flow cytometry (78.6%, P < 0.01) at 20 x 10(6) cells, as compared to PBS-treated mice (42.6%). In addition, yeast treatment elevated TNF-alpha and IFN-gamma plasma levels and lowered the elevated IL-10 levels. No adverse side effects from the yeast treatment were observed, including feeding/drinking cycle and life activity patterns. Indeed, yeast-treated mice showed significant final body weight gain (+21.5%, P < 0.01) at day 35. These data may have clinical implications for the treatment of solid cancer with yeast, which is known to be safe for human consumption.
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PMID:Saccharomyces cerevisiae, the Baker's Yeast, suppresses the growth of Ehrlich carcinoma-bearing mice. 1789 96

The present study has evaluated the immunogenicity of single or multiple Plasmodium falciparum (Pf) antigens administered in a DNA prime/poxvirus boost regimen with or without the poloxamer CRL1005 in rhesus monkeys. Animals were primed with PfCSP plasmid DNA or a mixture of PfCSP, PfSSP2/TRAP, PfLSA1, PfAMA1 and PfMSP1-42 (CSLAM) DNA vaccines in PBS or formulated with CRL1005, and subsequently boosted with ALVAC-Pf7, a canarypox virus expressing the CSLAM antigens. Cell-mediated immune responses were evaluated by IFN-gamma ELIspot and intracellular cytokine staining, using recombinant proteins and overlapping synthetic peptides. Antigen-specific and parasite-specific antibody responses were evaluated by ELISA and IFAT, respectively. Immune responses to all components of the multi-antigen mixture were demonstrated following immunization with either DNA/PBS or DNA/CRL1005, and no antigen interference was observed in animals receiving CSLAM as compared to PfCSP alone. These data support the down-selection of the CSLAM antigen combination. CRL1005 formulation had no apparent effect on vaccine-induced T cell or antibody responses, either before or after viral boost. In high responder monkeys, CD4+IL-2+ responses were more predominant than CD8+ T cell responses. Furthermore, CD8+ IFN-gamma responses were detected only in the presence of detectable CD4+ T cell responses. Overall, this study demonstrates the potential for multivalent Pf vaccines based on rational antigen selection and combination, and suggests that further formulation development to increase the immunogenicity of DNA encoded antigens is warranted.
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PMID:Induction of multi-antigen multi-stage immune responses against Plasmodium falciparum in rhesus monkeys, in the absence of antigen interference, with heterologous DNA prime/poxvirus boost immunization. 1792 26

Although B cells play a pathogenic role in the initiation of type 1 diabetes (T1D) in NOD mice, it is not known whether activated B cells can maintain tolerance and transfer protection from T1D. In this study, we demonstrate that i.v. transfusion of BCR-stimulated NOD spleen B cells into NOD mice starting at 5-6 wk of age both delays onset and reduces the incidence of T1D, whereas treatment initiated at 9 wk of age only delays onset of T1D. This BCR-activated B cell-induced protection from T1D requires IL-10 production by B cells, as transfusion of activated B cells from NOD.IL-10(-/-) mice does not confer protection from T1D. Consistent with this result, severe insulitis was observed in the islets of NOD recipients of transfused NOD.IL-10(-/-) BCR-stimulated B cells but not in the islets of NOD recipients of transfused BCR-stimulated NOD B cells. The therapeutic effect of transfused activated NOD B cells correlates closely with the observed decreased islet inflammation, reduced IFN-gamma production and increased production of IL-4 and IL-10 by splenocytes and CD4(+) T cells from NOD recipients of BCR-stimulated NOD B cells relative to splenocytes and CD4(+) T cells from PBS-treated control NOD mice. Our data demonstrate that transfused BCR-stimulated B cells can maintain long-term tolerance and protect NOD mice from T1D by an IL-10-dependent mechanism, and raise the possibility that i.v. transfusion of autologous IL-10-producing BCR-activated B cells may be used therapeutically to protect human subjects at risk for T1D.
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PMID:Intravenous transfusion of BCR-activated B cells protects NOD mice from type 1 diabetes in an IL-10-dependent manner. 1802 64

Surfactants like particles (SLP) are secreted by Intestinal epithelium. These particles have the ability to lower surface tension of intestinal epithelial cells and contain small amounts of surfactant specific proteins A, B, and D. In the intestinal lumen they are known to function as lubricants and/or as a vehicle to deliver digestive enzymes to the luminal fluid. These particles have been found to have the ability in binding of uropathogenic E.coli. But their immunological function is not known. The present study was designed to assess the role of the SLP in the regulation of immune response during Salmonella (S) typhimurium infection using a rat an enteric model. The animals were divided in four different groups including control (PBS), rats fed fat diet (corn oil), rats fed fat diet followed with S. typhimurium infection and rats with S. typhimurium infection alone. The Peyer's patches (PP), intraepithelial (IE) and lamina propria (LP) mononuclear cells were isolated from the above-mentioned groups. These mononuclear cells were then incubated in presence of S. typhimurium lysate alone, SLP alone and S. typhimurium lysate and SLP together. T cell markers CD4 and CD8, cytokines mainly pro-inflammatory ones including IFN-gamma, TNF-alpha, IL-12 etc were studied under such conditions. In addition histological studies were also carried out under these conditions. We report in this study that SLP plays an important role in modulating the cytokine level during infection. The pro-inflammatory cytokines were found significantly reduced in SLP induced diet along with the infection group compared to the infection group alone. Histopathological studies revealed the breakdown of duodenal villi after infection while only broadening of villi was observed in rats given corn oil induced SLP along with infection. These results suggested an important immuno-modulatory role for SLP during Salmonella infection.
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PMID:Immunoregulatory role of intestinal surfactant-like particles during Salmonella typhimurium infection. 1802 66


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